Enhanced antigen-specific antibody production following polyplex-based DNA vaccination via the intradermal route in mice

Kawase, Atsushi; Isaji, Keiko; Yamaoka, Ayumi; Kobayashi, Naoki; Nishikawa, Makiya; Takakura, Yoshinobu

doi:10.1016/j.vaccine.2006.04.056

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…According to Mohanan ( 33 ), intradermal injections of antigens generate higher IgG2a levels than intramuscular or subcutaneous routes. Also, skin is densely populated by immune-related cells such as keratinocytes capable of secreting immunostimulatory cytokines ( 34 ) and phagocytes that present antigens in secondary lymphoid organs and initiate an immune response of great magnitude ( 35 ). Second, horses of the study of Berglund and Schnabel ( 19 ) had ELA haplotypes determined and were known to be mismatched, whereas the exact matching conditions between the horses of our study are unknown.…”

Section: Discussionmentioning

confidence: 99%

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration

et al. 2022

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Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients’ sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections.

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Section: Discussionmentioning

confidence: 99%

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration

et al. 2022

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“…68 Indeed, TNF and IL1B are also strongly upregulated at 24 h in both polyplex-exposed samples, consistent with the characterization of HERC5 as a late inflammatory response gene. 68 TNFα was previously shown to be upregulated in keratinocytes in response to polyplex exposure, 69 and activation of TNFα and IL1β has been shown to be effected through TLRs, 38 which are also strongly affected here by the polyplex and polymer treatments. Interestingly, HERC5 has recently been shown to inhibit the replication of viral particles by blocking assembly, 70 and Gao et al 71 observed a 5-fold decrease in HERC5 by the same cell cycle array when human epidermal keratinocytes were treated with a fullerene derivative that induces cellular senescence.…”

Section: Table 2 Changes In Expression Ofmentioning

confidence: 98%

Polyplex Exposure Inhibits Cell Cycle, Increases Inflammatory Response, and Can Cause Protein Expression without Cell Division

et al. 2013

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We sought to evaluate the relationship between cell division and protein expression when using commercial poly(ethylenimine) (PEI)-based polyplexes. The membrane dye PKH26 was used to assess cell division, and cyan fluorescent protein (CFP) was used to monitor protein expression. When analyzed at the whole population level, a greater number of cells divided than expressed protein, regardless of the level of protein expression observed, giving apparent consistency with the hypothesis that protein expression requires cells to pass through mitosis in order for the transgene to overcome the nuclear membrane. However, when the polyplex-exposed population was evaluated for the amount of division in the protein-expressing subpopulation, it was observed that substantial amounts of expression had occurred in the absence of division. Indeed, in HeLa S3 cells, this represented the majority of expressing cells. Of interest, the doubling time for both cell lines was slowed by ~2-fold upon exposure to polyplexes. This change was not altered by the origin of the plasmid DNA (pDNA) transgene promoter (cytomegalovirus (CMV) or elongation factor-1 alpha (EF1α)). Gene expression arrays in polyplex-exposed HeLa S3 cells showed upregulation of cell cycle arrest genes and downregulation of genes related to mitosis. Chemokine, interleukin, and toll-like receptor genes were also upregulated, suggesting activation of proinflammatory pathways. In summary, we find evidence that a cell division-independent expression pathway exists, and that polyplex exposure slows cell division and increases inflammatory response.

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“…The predominant Th1 response to administration through the intradermal route was most likely due to the cooperation between Langerhans cells, the primary innate immune response cells and keratinocytes that may also be stimulated by the formulation. These elicited the production of cytokines and chemokines that helped in the activation of other APCs (52). …”

Section: Nps As Adjuvants To Generate Th1 and Th17 Responsesmentioning

confidence: 99%

Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development

2017

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Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen (Ag) immunogenicity, aiming to induce a protective and long-lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only seven have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines.

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Enhanced antigen-specific antibody production following polyplex-based DNA vaccination via the intradermal route in mice

Cited by 9 publications

References 44 publications

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration

Polyplex Exposure Inhibits Cell Cycle, Increases Inflammatory Response, and Can Cause Protein Expression without Cell Division

Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development

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